What is the link between endometriosis and infertility?

The Link Between Endometriosis and Infertility

Endometriosis affects at least one-third of women with infertility and up to 50% of women with endometriosis experience infertility, though the precise mechanisms remain incompletely understood. 1, 2, 3

Prevalence and Association

• Endometriosis is present in approximately one-third of infertile women, making it one of the most common identifiable causes of female infertility alongside ovulatory failure (21%) and tubal damage (14%). 1
• Up to 50% of women diagnosed with endometriosis will experience infertility, establishing a strong bidirectional association between the two conditions. 2, 3
• The disease affects approximately 10% of reproductive-aged women worldwide, representing an estimated 176 million women globally. 1, 2

Pathophysiological Mechanisms

The mechanisms linking endometriosis to infertility are multifactorial and include anatomical distortion, chronic inflammation, ovarian dysfunction, and impaired endometrial receptivity. 4, 5

Anatomical and Structural Factors

• Pelvic adhesions and fibrosis from endometriosis create anatomical distortions that mechanically interfere with ovum pickup by the fallopian tubes and normal tubal function. 4, 5
• Deep infiltrating endometriosis (lesions extending >5 mm beneath the peritoneal surface or involving bowel, bladder, ureter, or vagina) can cause severe anatomical disruption affecting reproductive organs. 1, 6
• Tubal occlusion and peritubular adhesions develop in women with a history of endometriosis-related pelvic inflammation, directly preventing fertilization. 1

Inflammatory and Immunological Mechanisms

• Chronic niche inflammation in the peritoneal cavity, ovaries, and uterus creates a hostile environment for conception through multiple pathways. 2, 4
• The inflammatory milieu produces cytokines and immune mediators that impair oocyte quality, sperm function, fertilization, and embryo development. 2, 4
• Endometriosis is fundamentally an estrogen-dependent inflammatory disease characterized by chronic inflammation that systemically affects reproductive function. 6, 7

Ovarian Dysfunction

• Endometriosis disrupts normal ovarian reserve and function, leading to ovulatory dysfunction even in women with regular menstrual cycles. 4, 5
• Ovarian endometriomas (endometriosis cysts) directly damage ovarian tissue and reduce the pool of viable follicles. 4
• The disease affects oocyte quality through inflammatory mediators and oxidative stress within the ovarian microenvironment. 2, 4

Endometrial and Implantation Defects

• Compromised endometrial receptivity represents a key mechanism, particularly in women with minimal or mild disease where anatomical factors are absent. 4, 3
• Endometrial changes associated with endometriosis create an inhospitable environment for embryo implantation, even when fertilization occurs successfully. 3
• The progesterone resistance characteristic of endometriosis impairs normal endometrial preparation for implantation. 6, 7

Clinical Implications

Heterogeneity of Presentation

• The population of infertile women with endometriosis is highly heterogeneous, with diverse phenotypes making it difficult to establish a single mechanism or predict individual fertility outcomes. 4
• The extent of disease (as measured by r-ASRM staging) correlates poorly with fertility outcomes, meaning severe anatomical disease does not necessarily predict worse fertility prognosis. 1, 6
• Women with minimal or mild peritoneal endometriosis may experience significant infertility despite minimal visible disease, suggesting inflammatory and molecular mechanisms predominate over anatomical factors in these cases. 3, 5

Assisted Reproductive Technology Outcomes

• Endometriosis is associated with poorer outcomes in assisted reproductive technology (ART), including decreased oocyte retrieval numbers, lower implantation rates, and reduced pregnancy rates compared to other causes of infertility. 2
• In vitro fertilization (IVF) remains effective for women with less-advanced endometriosis, achieving success rates similar to other infertility causes. 5
• Women with more advanced stages of endometriosis (stage III-IV) have demonstrably lower IVF success rates compared to those with minimal or mild disease. 5

Common Pitfalls in Understanding the Link

• Do not assume that the severity of pain symptoms correlates with the degree of infertility—these are independent manifestations of the disease with different underlying mechanisms. 1, 6
• Avoid concluding that absence of visible endometriosis on imaging or laparoscopy rules out endometriosis-associated infertility, as small peritoneal implants causing significant inflammatory effects are poorly detected by current imaging modalities. 1
• Do not overlook that approximately 28% of infertile couples have unexplained infertility, and undiagnosed minimal endometriosis may account for a substantial portion of these cases. 1

Systemic Nature of the Disease

• Endometriosis should be understood as a systemic disease rather than solely a pelvic condition, with multifactorial etiology including genetic factors, possible epigenetic influences, and environmental exposures. 1, 6
• The disease exhibits hormone-responsive behavior with estrogen-dependence and progesterone resistance, maintaining itself through autonomous local estrogen synthesis independent of ovarian production. 6, 7
• This systemic inflammatory state has pleiotropic direct and indirect effects on reproduction that extend beyond localized pelvic pathology. 4